The GNB3 C825T polymorphism influences platelet aggregation in human whole blood

BACKGROUND: Platelet aggregation varies among individuals; and genetic factors may alter platelet activation through G-protein-coupled receptors, thus influencing results of point-of-care platelet aggregometry in whole blood. We tested the hypothesis that the C825T polymorphism of the gene GNB3 encoding the G-protein β-3 subunit and the platelet GPIIIa Pl(A1)/(A2) polymorphism of the glycoprotein IIIa influence platelet aggregation. METHODS: Evoked [thrombin receptor activating peptide (TRAP), ADP, TXA(2) agonist U46619, epinephrine, and collagen] platelet aggregation in whole blood was measured using impedance aggregometry (Multiplate) in 143 healthy individuals (age: 40.2 years ±11.7 SD). Genotypes were determined using pyrosequencing and restriction analysis. Data were analyzed by linear one-way analysis of variance and Student's t-test, linear and multiple regression, and the χ(2)-test, as appropriate. RESULTS: Homozygous carriers of the GNB3 825C-allele showed significantly (P≤0.022) increased maximum aggregation for EC(75) dosages compared with CT and TT genotypes [e.g. ADP: CC 150±36 vs. TT 126±33 aggregation unit (AU); thrombin receptor activating peptide: CC 175±46 vs. TT 150±38 AU; U46619: CC 164±33 vs. 149±32 AU; epinephrine: CC 66±41 vs. TT 48±34 AU]. In contrast, genotypes of glycoprotein IIb/IIIa PI(A)-polymorphism had no effect. Regression analysis revealed the GNB3 C825T polymorphism as an independent factor for enhanced platelet aggregation, besides factors such as female sex and blood cell values. CONCLUSION: In human whole blood, the GNB3 825CC genotype is associated with enhanced platelet aggregation.